Objective ·To investigate the immunotherapeutic effects of exosomes derived from leukemia cells with high expression of B7 molecules (co-stimulatory molecules CD80 and CD86) in tumor-bearing mice. Methods ·L1210 leukemia cells were transfected with lentiviral vectors containing the CD80 and CD86 genes, and thereby the leukemia cells with high expression of CD80 and CD86 molecules were obtained. Exosomes LEX-8086 with high expression of CD80 and CD86 molecules were then isolated from the culture supernatant. The biological characteristics of LEX-8086 were analyzed by using transmission electron microscopy (TEM) and Western blotting. A DBA/2-leukemia tumor-bearing mouse model was established. The tumor-bearing mice were divided into LEX-8086 group and PBS group. The LEX-8086 group received intravenous injections of 500 μL LEX-8086 (150 μg/mL) via the tail vein 7 d and 12 d after tumor cell inoculation, while the PBS group received injections of equal volumes of PBS at the same time points. Differences in body weight, tumor volume, tumor mass, and survival of the mice between the two groups were observed. Flow cytometry was used to analyze the changes in the immune cells in spleens and lymph nodes of the mice in both groups. Western blotting and real-time fluorescent quantitative PCR (qPCR) were used to detect the expression of markers for M1 and M2 macrophages in the spleens of the mice in both groups. Results ·The exosomes LEX-8086 were isolated from the supernatant of L1210 cells overexpressing CD80 and CD86 molecules. TEM revealed that LEX-8086 exhibited a disc-shaped vesicular structure with a diameter of approximately 100 nm. Western blotting demonstrated the expression of exosome-specific markers. In the animal experiments, compared with the PBS group, the body weight of the LEX-8086 group showed no significant change, while both the tumor volume and the relative tumor mass ratio decreased significantly, and the survival was significantly prolonged (all P<0.05). Flow cytometry results indicated that the proportions of natural killer (NK) cells and CD4⁺ T cells in the lymph nodes and spleens of the LEX-8086 group significantly increased (all P<0.05); as for CD8⁺ T cells, they only increased in the lymph modes (P=0.012). Moreover, flow cytometry results showed that the proportion of M1 macrophages in the spleens of mice in the LEX-8086 group was significantly elevated (P=0.003), while the proportion of M2 macrophages remained unchanged. Western blotting and qPCR also revealed that the mRNA and protein expression levels of M1 macrophage markers interleukin-6 and tumor necrosis factor-α in the spleens of mice in the LEX-8086 group increased significantly (all P<0.05). Conclusion ·Exosomes derived from leukemia cells with high expression of co-stimulatory molecules CD80 and CD86 can induce a therapeutic anti-leukemic effect, which may be achieved by increasing the proportions of NK cells, M1 macrophages, CD4⁺ T cells, and CD8⁺ T cells.

Objective ·To explore the metabolic profiling and metabolic reprogramming patterns of lung cancer cells with acquired resistance to sotorasib, a specific inhibitor to KRAS. Methods ·The H2122 and H358 lung cancer cell models with acquired resistance to sotorasib (H2122-SR and H358-SR cells) were established and validated by CCK-8 assay. Ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was employed to acquire the metabolic profiling of the resistant lung cancer cells and their homologous parental cells. Untargeted metabolomics studies and metabolic characterizations were conducted with multi-dimensional methods, including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), to identify differential metabolites associated with acquired resistance to sotorasib. Then these differential metabolites were subjected to pathway enrichment analysis. Heatmap analysis was used to compare the changes in metabolites in major differential metabolic pathways between the resistant and parental cells. Results ·The cell models of H2122 and H358 with acquired resistance were successfully constructed, with half-maximal inhibitory concentrations (IC₅₀) of sotorasib being 50 times higher than those of the parental cells. Besides, the metabolic profiling was significantly different between the resistant and parental cells. A total of 48 differential metabolites were identified between H2122-SR and H2122 cells. The top 10 differential metabolites, ranked by VIP values, were uridine, xanthylic acid, indole-3-carboxylic acid, nicotinic acid, xanthosine, xanthine, N-methylnicotinamide, hypoxanthine, trigonelline, and galactonic acid. Between H358-SR and H358 cells, a total of 79 differential metabolites were identified. The top 10 differential metabolites, ranked by VIP values, were glutathione, xanthosine, 2-ketoglutaric acid, carboxyethyl lysine, thymidine, purine, riboflavin, 3-indoleacrylic acid, indole-3-pyruvic acid, and dihydrouracil. The differential metabolites in the two lung cancer cell lines mainly participated in purine metabolism and glycolysis/gluconeogenesis, and purine metabolism was the most significantly altered metabolic pathway. Heatmap analysis showed that many metabolites in the purine metabolism were elevated in the sotorasib-resistant cells. Conclusion ·The lung cancer cells with acquired resistance to sotorasib show enhanced purine metabolism.

Objective ·To investigate the expression of serpin family E member 1 (SERPINE1) in gastric cancer and its potential mechanisms in promoting gastric cancer. Methods ·Pan-cancer analysis of SERPINE1 was performed by using the TIMER2.0 online website, and the differences in the expression of SERPINE1 in samples with different tumor stages of gastric cancer were analysed by the clinical data of gastric cancer from The Cancer Genome Atlas (TCGA) database. Survival curves were plotted. Quantitative real-time PCR (qRT-PCR) was used to detect mRNA expression in paired samples of clinical gastric cancer tissues. The small interfering RNA (siRNA) transfection technique was used to knock down the expression of SERPINE1 in MGC-803 and SGC-7901 gastric cancer cell lines, and the migration and invasive abilities of gastric cancer cells were investigated by Transwell and invasion chamber experiments. The effects of SERPINE1 knockdown on the angiogenesis of gastric cancer cells were further explored by the migration assay of human umbilical vein endothelial cells (HUVEC) and tubule formation assay of HUVECs. The Gene Expression Omnibus (GEO) dataset was used for differential gene analysis in high and low expression groups based on the median value of SERPINE1 expression. The differentially expressed genes were further analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA). qRT-PCR was performed to verify the expression levels of key genes related to epithelial-mesenchymal transition (EMT) and angiogenesis. Results ·Bioinformatics analysis showed that SERPINE1 was highly overexpressed in a variety of primary tumour tissues, including gastric cancer. SERPINE1 gene expression increased with increasing tumour stage (P<0.001), and increased expression of SERPINE1 was associated with poor prognosis of gastric cancer (P<0.001). qRT-PCR results showed that SERPINE1 was significantly highly expressed in gastric cancer tissues (P=0.038). After knocking down SERPINE1, gastric cancer cell lines MGC-803 and SGC-7901 cells had decreased migration and invasion (P<0.05). Gastric cancer culture supernatants from the SERPINE1-knockdown gastric cancer cell line reduced angiogenesis in HUVECs (P<0.05). Differential genes in gastric cancer patients in the SERPINE1 high-expression group in the GEO database were enriched in cancer-related pathways such as focal adhesion, extracellular matrix receptor interaction, and angiogenesis-related pathways like angiogenesis and the vascular endothelial growth factor (VEGF) signalling pathway. The expression of SERPINE1 was negatively correlated with cadherin 1 (CDH1), and positively correlated with other key genes related to EMT and angiogenesis. Moreover, the expression levels of key genes related to EMT and angiogenesis detected by qRT-PCR in SERPINE1 knockdown gastric cancer cell lines (P<0.05), were consistent with the correlation analysis results mentioned above. Conclusion ·SERPINE1 expression is elevated in gastric cancer tissues, which could regulate the expression levels of key genes related to EMT and angiogenesis to promote the migration, invasion and angiogenesis of gastric cancer cells.

Objective ·To explore the effects and potential molecular mechanisms of blocking cannabinoid receptor 1 (CB1) in acute lung injury (ALI) in mice. Methods ·Forty mice were randomly divided into blank control group, AM281 (CB1 antagonist) control group, lipopolysaccharide (LPS) group, and LPS＋AM281 group, with ten mice in each group. ALI models were induced by LPS. The pathological manifestations of lung tissues were observed in each group of mice by hematoxylin and eosin (H-E) staining and the inflammation scores were calculated. The mRNA levels of M1 markers [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-12] and M2 markers [arginase (Arg), mannose receptor, C type 2 (Mrc2), macrophage galactose-type lectin 1 (Mgl1)] in lung macrophages were measured by reverse transcription and real-time fluorescence quantitative polymerase chain reaction (qPCR). Human myeloid leukemia monocytes THP-1 cells were cultured in vitro, and the expression of CB1 and CB2 in THP-1 cells was detected by immunofluorescence. After further blocking CB1 and inhibiting the Gα_i/o/RhoA signaling pathway, the mRNA levels of M1 markers were assessed. Results ·The LPS group showed significant lung tissue damage and a significant increase in inflammation scores in mice. After blocking CB1, compared with the LPS group, the LPS＋AM281 group of mice showed improvements in lung injury, manifested as improved congestion of alveolar wall capillaries, reduced infiltration of inflammatory cells in the lung interstitium and alveolar cavity, and a decreased inflammation score (P=0.007). Compared with the control group, the levels of M1 marker in the lung tissue of the LPS group were upregulated, while the polarization of macrophages changed and the M1/M2 ratio was reversed after blocking CB1 (all P<0.05). In vitro studies found that macrophages expressed CB1 and CB2. Activation of CB1 by arachidonyl-2-chloroethylamide (ACEA) upregulated the expression of M1 markers. Blocking CB1 and selectively inhibiting Gα_i/o/RhoA signaling significantly downregulated M1 markers (all P<0.05). Conclusion ·CB1 promotes the polarization of macrophage towards the M1 phenotype through the Gα_i/o/RhoA signaling pathway in ALI, and blocking CB1 can improve lung injury.

Objective ·To explore the diagnostic, therapeutic, and prognostic value of metagenomics next-generation sequencing (mNGS) in patients with pneumonia-induced sepsis. Methods ·This study consisted of a multicenter, prospective, non-randomized controlled trial and a diagnostic test. Patients with pneumonia-induced sepsis who were hospitalized in four hospitals across China were enrolled between March 2020 and October 2021. All patients met the Sepsis-3 criteria issued by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine, as well as the clinical diagnostic standard of pneumonia. Enrolled patients were assigned based on their preference to either the conventional test-only group [receiving only conventional test (CMT)] or the combined mNGS test group (receiving CMT and mNGS concurrently). The primary outcome was the 7-day all-cause mortality rate, and secondary outcomes included the changes in SOFA and APACHE Ⅱ scores from baseline to day 7, 28-day all-cause mortality rate, the composite endpoint of mechanical ventilation or death within 28 d, 28 d ventilation-free days, 28 d hospital-free days, and the average daily hospitalization cost. Propensity score matching was used to balance covariates between the two groups. Kaplan-Meier curves were plotted and Cox proportional hazards models were built to compare the risk of death between the two groups. Pathogen detection results from infection site samples in the combined mNGS test group were used for the diagnostic test. The clinically-adjudicated causative pathogens was used as the reference standard. The results of traditional pathogen detection and mNGS detection were compared respectively with the reference standard. The positive percent agreement, negative percent agreement, positive predictive value, and negative predictive value between the two methods and the reference standard were calculated. McNemar's χ² test was used to evaluate the causative pathogen detection capabilities of the two methods. Results ·A total of 533 patients were enrolled, of whom 311 opted for additional mNGS testing, while 222 received only conventional pathogenetic testing. In the non-randomized controlled trial, after propensity score matching to balance covariates, the 7-day all-cause mortality was lower in the combined mNGS test group compared to the conventional test-only group [4.8% vs 8.6%, HR 0.37 (95%CI 0.15‒0.91), P=0.031]. Additionally, the 28-day ventilation-free days were increased in the combined mNGS test group (19.9 d vs 18.4 d, P=0.041). No significant difference was observed between the two groups in terms of 28-day all-cause mortality or the average daily hospitalization costs. In the diagnostic test, compared to the reference standard, the positive percent agreement of mNGS with the clinical composite judgment for causative pathogens was higher than that of CMT [91.9% (95%CI 87.7%‒95.0%) vs 56.1% (95%CI 49.7%‒62.4%), P<0.001]. Conversely, the negative percent agreement of mNGS was lower than that of CMT [29.2% (95%CI 18.6%‒41.8%) vs 69.2% 95%CI 56.6%‒80.1%), P<0.001]. The negative predictive value of nNGS was higher than that of CMT [48.7%(95%CI 32.4%‒65.2%) vs 29.4% (95%CI 22.3%‒37.3%), P=0.001]. Conclusion ·In patients with pneumonia-induced sepsis, mNGS of infection site samples demonstrated a higher detection rate of causative pathogen compared to CMT. Furthermore, the combination of mNGS with CMT may help reduce the 7-day all-cause mortality, suggesting that mNGS has clinical value and potential for application in the management of sepsis caused by pulmonary infections.

Objective ·To compare the effects of calcium hydroxide (CH) residues in root canals and root canal filling methods on apical closure, and to provide reference for clinical selection of root canal sealing drugs and filling methods. Methods ·Seventy-five permanent mandibular premolar teeth with single root canals that were extracted due to orthodontic treatment or periodontal problems were collected from the Department of Oral and Maxillofacial Surgery of the Affiliated Hospital of Qingdao University. The crowns were removed, the root canals were prepared, and the specimens were randomly assigned into 3 groups: a water-soluble calcium hydroxide group (Group A, n=30), an oil-soluble calcium hydroxide group (Group B, n=30), and an unsealed control group (Group C, n=15). After 2 weeks of sealing, Groups A and B underwent manual preparation with a #35 K-file, followed by ultrasonic agitation and irrigation of the root canal to ensure that the calcium hydroxide residue was located roughly at the root apex and that the residue was 15% to 20%. Groups A, B, and C were randomly divided into 3 groups: the iRoot SP single-tip group (Group 1), the hot compression group (Group 2), and the cold compression group (Group 3), and root canals were filled using the iRoot SP single-tip method, the hot adhesive vertical compression filling method, and the cold adhesive lateral compression filling method, respectively. A dye penetration test was used to evaluate apical microleakage, and scanning electron microscopy was used to observe the microscopic morphology of the dentin-root canal sealer interface in each group. Statistical analysis was performed using two-way ANOVA. Results ·Both root canal sealing drugs and root canal filling methods affected the apical sealing, and there was an interaction between them. The effects of residual calcium hydroxide on apical closure were analyzed. The difference between Group B and Group C was statistically significant only in Group 1. There were statistically significant differences between Group A and Group C in Group 2 and Group 3, and statistically significant differences between Group A and Group B regardless of the root filling method. Among the three root filling methods, there was a statistically significant difference between Group 1 and Group 3 in Group C (P=0.013). In Group A and Group B, there were statistically significant differences between Group 2, Group 3 and Group 1 (P<0.001). Conclusion ·The residual water-soluble calcium hydroxide in the root canal has a negative effect on the apical closure, but the residual oil-soluble calcium hydroxide has a small negative effect on the apical closure. iRoot SP can reduce the negative effect of residual water-soluble calcium hydroxide on root canal closure.

Objective ·To explore the value of combined diaphragm and intercostal muscle ultrasound assessment compared with conventional diaphragm ultrasound in predicting the weaning outcome in mechanically ventilated patients with sepsis. Methods ·Mechanically ventilated patients with sepsis, consecutively admitted to the Department of Critical Care Medicine of Affiliated Hospital of Nantong University from October 2022 to December 2023, were selected. During the peri-weaning period, after the patient's sepsis condition improved and the patient passed the spontaneous breathing trial (SBT), ultrasound evaluation of respiratory muscles was performed by ultrasound qualified personnel with ultrasound qualification and experience in bedside ultrasound examination. Diaphragm excursion (DE), thickening fraction of diaphragm (TFD), and thickening fraction of intercostal muscle (TFic) were measured, respectively. The patients were divided into a successful weaning group (n=114) and a failed weaning group (n=24) according to the weaning results. Receiver operating characteristic (ROC) curves were used to analyze the value of diaphragm ultrasound and intercostal muscle ultrasound, alone and in combination, in predicting ventilator weaning outcome. Results ·TFic and TFic/TFD were significantly higher in the failed weaning group during SBT than in the successful weaning group (all P<0.05). The areas under the ROC curve (AUROC) of DE, TFD, and TFic to predict weaning failure in mechanically ventilated patients with sepsis during the period of SBT were 0.689 (0.591‒0.776), 0.657 (0.557‒0.747), and 0.769 (0.676‒0.846), respectively, whereas the combined indexes TFic/TFD and TFic&TFD_mix had AUROCs of 0.867 (0.786‒0.925) and 0.860 (0.778‒0.920), respectively. TFic/TFD with a cutoff value of >0.95 had a sensitivity of 86.7% and a specificity of 75.3% in predicting weaning failure, and TFic&TFD_mix with a cutoff value of >0.13 had a sensitivity of 86.6% and a specificity of 80.9% in predicting weaning failure. Moreover, the intercostal muscle ultrasonography method had an intra-observer intraclass correlation coefficient (ICC) of 0.890 and an extra-observer ICC of 0.876 for measurement reliability, which were both rated as good (P<0.001). Conclusion ·Combined diaphragm and intercostal muscle ultrasonography provides a more comprehensive picture of the patient's overall respiratory muscles, and has a higher guiding value in predicting the weaning outcomes in mechanically ventilated patients with sepsis than diaphragm ultrasound alone.

Objective ·To retrieve and evaluate evidence related to weight management during endocrine therapy for prostate cancer patients, and summarize the best evidence available. Methods ·The PIPOST model was adopted to construct evidence-based questions. Following the “6S” model of evidence resources, a systematic computer-based search was conducted to retrieve relevant evidence on weight management during prostate cancer endocrine therapy from various databases and websites, including Guidelines International Network, BMJ Best Practice, UpToDate, JBI Evidence-Based Healthcare Center Database, American Guidelines Network, Medlive, Cochrane Library, PubMed, CINAHL, Web of Science, Embase, CNKI, Chinese Biomedical Literature Database, Wanfang Database, and VIP Database, as well as the websites of the American Urological Association, European Urological Association, and Urological Branch of Chinese Medical Association. The evidence retrieved included guidelines, clinical decisions, recommended practices, expert consensuses, evidence summaries, systematic reviews, and original studies. The search period spanned from database establishment to December 2023. Two researchers independently evaluated the quality of the included literature. The included articles were read one by one and summarized according to themes. Priority was given to high-level, high-quality, and newly published authoritative literature during evidence screening and extraction. The included and extracted evidence was uniformly classified into levels 1‒5 according to the JBI evidence pre-classification and evidence recommendation level system, and the evidence recommendations were divided into strongly recommended (Grade A) and weakly recommended (Grade B). Results ·A total of 12 articles were retrieved, consisting of 4 guidelines, 3 expert consensuses, 2 evidence summaries, 2 randomized controlled trials, and 1 quasi-experimental study. All 12 articles were rated as high quality and were included. The best evidence was summarized into 8 aspects: weight management assessment and monitoring, multidisciplinary collaboration, personalized support, family involvement strategies, nutrition management strategies, exercise management strategies, health education, and follow-up management. Conclusion ·The best evidence for weight management during endocrine therapy for prostate cancer is summarized into eight aspects. In clinical application, specific clinical situations and patient characteristics should also be considered to improve the effectiveness of clinical interventions and the quality of care.

Objective ·To investigate the causal relationship between type 2 diabetes mellitus (T2DM) and cognitive dysfunction using two-sample Mendelian randomisation (MR). Methods ·Instrumental variables associated with T2DM were pooled from a large-scale genome-wide association study (GWAS) dataset. Inverse variance weighting was used as the primary analytical technique, supplemented by MR-Egger regression, weighted median and simple median analyses. Meta-analysis was jointly applied to combine different endpoints and to analyse the possibility of a causal relationship between T2DM and dementia, Alzheimer's disease, and Parkinson's dementia. Horizontal pleiotropy was examined by MR-PRESSO global test and MR-Egger analysis. Results ·There was a causal relationship between genetically predicted T2DM and dementia (OR=1.11, 95%CI 1.02~1.20, P=1.96×10^-2) and AD (OR=1.16, 95%CI 1.04~1.30, P=8.41×10^-3). Meta-analysis also supported the association between T2DM and cognitive impairment (OR=1.12, 95%CI 1.05~1.20, P=4.22×10^-4). A series of sensitivity analyses suggested the absence of heterogeneity and horizontal pleiotropy. Reverse MR analysis showed no significant causal relationship of various types of dementia on T2DM. Conclusion ·T2DM is positively associated with the risk of developing various types of dementia, suggesting that T2DM may be an important risk factor for cognitive impairment.

Objective ·To establish a research framework for serotonylation of proteins and to provide a methodological basis for the identification of serotonylated proteins. Methods ·The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression of the transglutaminase 2 (TGM2) gene, which encodes the key enzyme for serotonylation, and the solute carrier family 6 (SLC6A4) gene, which encodes the serotonin transporter (SERT), in normal and pan-cancer tissues. 5-Propargyltryptamide (5-PT), a serotonin derivative, was synthesized stepwise from serotonin hydrochloride, and its structure was characterized by the Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR), carbon nuclear magnetic resonance (¹³C-NMR), and time-of-flight mass spectrometry (TOF-MS). The intracellular uptake of 5-PT in the human pancreatic cancer cell line AsPC-1 and mouse immune cells, including CD4⁺ T cells, CD8⁺ T cells, and bone marrow-derived macrophages (BMDMs), was detected by using flow cytometry. Click chemistry, co-immunoprecipitation, and mass spectrometry analysis techniques were employed to identify serotonylated proteins, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed. Results ·Bioinformatics analysis indicated that TGM2 and SLC6A4 were widely expressed in various normal tissues and across pan-cancer tissues. The flow cytometry results showed that the synthesized 5-PT can be taken up into the human pancreatic cancer cell line AsPC-1 and mouse immune cells, including CD4⁺ T cells, CD8⁺ T cells, and BMDMs, via the SERT. Mass spectrometry analysis data showed that a significant amount of serotonylated proteins were enriched in various cells treated with 5-PT. KEGG enrichment analysis revealed that these proteins were involved in important pathways related to glycolysis and amino acid synthesis. Conclusion ·By using the synthesized 5-PT, multiple serotonylated proteins are enriched in various cell types. A research system for identifying serotonylated proteins has been successfully established, providing a relatively simple and efficient method for studying protein serotonylation.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder starting from early childhood. At present, the age of diagnosis for ASD in children is significantly delayed, typically occurring after two years of age, although behavioral signs or prodromal symptoms can emerge before the age of 12 months. These early indicators gradually evolve into the core symptoms of ASD. It has been well recognized that early screening and intervention can maximally improve its prognosis and promote optimal development of the affected children. Therefore, there has been increasing emphasis on preemptive screening and intervention for prodromal symptoms of ASD before the age of 12 months in clinical practice and research, so as to reduce the symptoms to a normal state to some extent. However, during the prodromal period of ASD, especially before the age of one, preemptive screening and intervention present many challenges. Preemptive screening faces obstacles such as significant individual differences in infant growth and development, incomplete presentation of ASD symptoms, and differing assessment content and criteria; preemptive intervention must overcome challenges like the diversity of screening tools and varying factors of parents. As a result, few research has been conducted in this field. This review mainly introduces preemptive screening tools and intervention techniques for children with ASD in the first year of life, including the intervention used in the British Autism Study of Infant Siblings-video interaction for promoting positive parenting (iBASIS-VIPP), the promoting first relationships, the environmental enrichment for infants, parenting with acceptance and commitment therapy (ENACT), and the adapted response teaching. The application of neuroimaging technology and artificial intelligence technology is also explained to provide reference for relevant research and clinical practice.

Skin malignancies include non-melanoma skin cancers and melanoma, with high incidence rates that pose a significant burden on public health and healthcare systems. Research in this area is crucial. Ultraviolet radiation (UV) is recognized as the primary risk factor for skin malignancies, with its main carcinogenic mechanism involving UV-induced DNA damage, which leads to the accumulation of mutations in key oncogenes and tumor suppressor genes. This accumulation promotes malignant transformation of related cells, ultimately resulting in the formation of malignant tumors. Understanding the specific processes through which UV-induced DNA damage contributes to the development of skin malignancies is crucial for advancing related research. Therefore, this paper focuses on the mechanisms of UV-induced DNA damage, the repair mechanisms for UV-induced DNA damage, and the relationship between UV-induced DNA damage and the occurrence of the three major types of skin malignancies.

Cutaneous melanoma (CM) is a highly malignant tumor caused by malignant proliferation of melanocytes, characterized by distant metastasis and high mortality. Although targeted therapy and immunotherapy have significantly improved the survival rates of advanced CM patients, tumor resistance remains a key barrier to further improving treatment outcomes. In recent years, significant progress has been made in the study of autophagy as a key regulatory cell death mode in the pathogenesis of CM. Autophagy is the main mechanism that mediates the degradation and recycling of various cellular components through lysosomes to maintain the homeostasis of the intracellular environment. A large number of studies have confirmed that the role of autophagy in CM is complex and controversial. In the early stages of CM development, autophagy may inhibit abnormal proliferation of tumor cells by removing damaged cell components. However, as the tumor progresses, autophagy may transform into a role that promotes tumor invasion and metastasis. In advanced CM, the activation of autophagy helps tumor cells survive in stressful environments. In particular, in CM with BRAF (V-Raf murine sarcoma viral oncogene homolog B1) mutations, autophagy activity is often enhanced, weakening the effectiveness of BRAF inhibitor-targeted therapy. This article provides an in-depth analysis of the dual effects of autophagy on the progression of CM and explores the role of autophagy in CM resistance, in order to provide insights for the development of new targeted therapy strategies for CM.

Diabetes is a common endocrine and metabolic disorder, with its prevalence steadily increasing, particularly in China. It is often associated with a range of complications, among which diabetic bladder dysfunction (DBD) is prevalent but frequently overlooked, significantly impacting patients' quality of life. Although much is known about diabetes-related complications, the pathogenesis of DBD remains unclear. Recent studies have highlighted the critical role of oxidative stress in the development and progression of DBD. This review first introduces the relationship between oxidative stress and diabetic complications, detailing how oxidative stress is generated and its underlying mechanisms under hyperglycemic conditions. It then focuses on the link between oxidative stress and DBD, explaining how oxidative stress induced by diabetes leads to urothelial dysfunction, reduced detrusor muscle contractility, and neuronal degeneration, ultimately impairing bladder function. Recent animal studies have demonstrated promising results of antioxidant treatments in ameliorating DBD. Additionally, this review discusses the advances in antioxidant nanomaterials for the treatment of diabetic complications and their potential applications in DBD therapy. Based on these findings, the review aims to provide theoretical support for clinical research and guide future directions in antioxidant-based therapies for DBD.

Mental disorders frequently co-occur with other physical illnesses, becoming one of the leading causes of disability worldwide. Early diagnosis and intervention are crucial for the effective management of these disorders. Currently, biomarker studies on mental disorders predominantly concentrate on genes, blood indicators, and imaging features of the brain. There is a growing interest in objective phenotypic markers as a research focus. It is established that the retina is part of the central nervous system (CNS), which extends from the mesencephalon and develops concurrently with the brain during the embryonic period. Given the overlapping pathophysiological mechanisms between neurodegenerative diseases and mental disorders, studying the structural and functional changes in the inner layers of the retina has emerged as a new direction in mental health research. The advent of optical coherence tomography (OCT) has enabled microscopic imaging of retinal structures. OCT is capable of objectively quantifying the retinal sub-layers and offers the advantages of being non-invasive, non-contact, and high-resolution. The use of OCT to explore structural changes in the retina among individuals with schizophrenia, bipolar disorder, major depression and other psychiatric disorders has been well documented; however, there is a paucity of reviews on this topic. This review summarizes current research on retinal structural alterations in patients with mental disorders, and the results demonstrate reduced thickness in certain sub-layers of the retina structure in patients with several mental disorders, which supports that the retina structure has the potential to be a biomarker for mental disorders and offers a novel avenue for research in the diagnosis and treatment.